The long-term objective is to determine whether exposure to different exogenous mutagens are responsible for differences in the incidence and prognosis of breast cancer in ethnically and racially diverse populations. The approach is to compare the specific biochemical pattern of mutation in the tumor suppressor gene, p53, in breast cancers from populations with low incidence of breast cancer, Japanese and native Americans, to the pattern of mutation in populations with a high incidence of breast cancer, northern Europeans and North Americans. Ethnically diverse groups within North America including a midwestern Caucasian and midwestern Black population will also be compared. Methodology has been developed which permits direct sequencing of most of the p53 genome from pure clusters of cancer cells isolated from touch preparations of fresh or frozen tissue. This technology makes a molecular epidemiological approach to human breast cancer feasible because it can be applied to unselected tumor specimens and does not significantly compromise use of the same sample for other purposes. Precise definitions of patterns of mutation in populations at high and low risk for breast cancer may help to distinguish between endogenous and exogenous processes contributing to the development of this cancer.